The two major research aims of our ongoing studies of the effects of high altitude on CNS development and function are to clarify the cellular and molecular mechanisms by which hypoxia impairs brain maturation and to identify CNS-endocrine interrelations during critical stages of brain development. With respect to the first inquiry, work in progress in 1975 has specifically investigated the timetable of development for proteins in myelin and for synthesizing and catabolizing enzymes for biogenic amines in selected brain areas and the alterations which may occur in this timetable when the animals are born and reared at high altitude. Our preliminary findings indicate impaired development of these constituents and validate the hypothesis that both myelinogenesis and neurotransmission are affected by hypoxia. Parallel studies on our second inquiry concerned with CNS-endocrine relationships disclose that the alterations in reproductive function observed in adult rats maintained at high altitude may reflect impaired development of hypothalamo-pituitary relationships. Our observations indicate that the development of gonadotropins (measured by radioimmunoassay) is altered under conditions of hypoxia (either natural, at high altitude, or simulated in decompression chambers) with respect to the total plasma and pituitary levels of these hormones, their developmental pattern and particularly their ratio at specific ages particularly critical for maturation of the reproductive function. In addition, evidence is also accumulating that alterations in gonadotropic levels observed in the hypoxic animals may be associated with disturbances in CNS biogenic amine levels and metabolism. Finally, our continuing studies on the role of thyroid hormones on brain development at sea level and at high altitude suggest that the maturation of the hypothalamo-pituitary-thyroid axis is altered in rats developing at high altitude. BIBLIOGRAPHIC REFERENCE: Petropoulos, E.A. and Timiras, P.S.: Development of hypophyseal function in rats at high altitude. Fed. Proc., 34:411, 1975.